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K A Martin

Publications and source records attributed to K A Martin.

At least 19 recordsLinked to original sources
PubMed1992

Synaptic connections of physiologically identified geniculocortical axons in kitten cortical area 17.

Single geniculocortical axons were recorded in the cortical white matter of kittens and adult cats by using micropipettes filled with horseradish peroxidase (HRP). Of 41 axons recovered in 4-5 week old kittens, three well-filled axons arborized in area 17; the remainder were incomplete or arborized in area 18. One axon had Y-like physiological properties, two were X-like. They were recovered from two 34-day-old kittens. All three axons formed clustered arborizations, mainly in layer 4A. Electron microscopic (EM) analysis of 50 boutons from kitten and 38 boutons from adult controls revealed that the boutons from kitten made synapses more frequently on spines (91% of targets) than did the boutons from the adult (71%). One X-like axon in kitten also had a collateral projection that made synapses in layer 1; this has not been seen in adult cats. In overall extent, the axons from kitten fell within the adult range.

Aging↗
PubMed1992

The mas proto-oncogene is developmentally regulated in the rat central nervous system.

The mas proto-oncogene encodes a protein with a predicted structure similar to members of the family of seven transmembrane domain spanning receptors. These receptors are thought to transduce extracellular signals to G-proteins. Angiotensin II and III have been reported to be the functional ligands for the mas oncogene-encoded receptor (Jackson et al., 1988). We show here using in situ hybridization histochemistry and RNase protection assays that mas mRNA is expressed in a subpopulation of neurons in both the adult and developing rat CNS. In the adult CNS, mas mRNA is most abundant in hippocampal pyramidal neurons and dentate granule cells; mas transcripts are also present at low levels in the cortex and thalamus. mas is first expressed in the developing rat CNS at postnatal day 1 (P1). Even at this early stage in CNS development the pattern of mas expression is similar to that seen in the adult. Although at P1 most neurons of the dentate gyrus are not yet generated and cells of the hippocampal CA fields are undergoing migration and synaptogenesis (Bayer 1980; Altman and Bayer, 1990a, 1990b, 1990c), mas is specifically expressed in these cell populations. This extremely restricted pattern of expression suggests that mas may function in determining the morphology and connections of specific cell types in the hippocampus. This function may in part be carried out by the ability of mas to link external cues to intracellular processes.

Animals↗
PubMed1992

The neurons in layer 1 of cat visual cortex.

We have examined the morphology of neurons in layer 1 by injecting them intracellularly with lucifer yellow in lightly fixed brain slices (250 microns thick) taken from the medial bank of area 17 in adult cats. Of 22 neurons with well-filled dendrites, 16 had smooth dendrites, two had sparsely spiny dendrites (less than 200 spines) and, unexpectedly, four had spiny dendrites typical of pyramidal cells. The axon was generally not well filled. Computer reconstructions showed that parts of the dendritic tree had been lost in the sectioning. Nevertheless, measurements of the length of intact dendrites suggested an average diameter of the dendritic tree of 220 microns. The density of the neurons was such that the dendritic trees of about six neurons cover each point in layer 1. Thus, despite the very low density of neurons that characterizes layer 1, there are more than sufficient neurons to sample from the entire representation of the visual field in area 17.

Animals↗
PubMed1992

Odors can induce feeding motor responses in the terrestrial mollusc Limax maximus.

Highly developed odor learning was shown in the terrestrial slug Limax maximus. In addition, several key cellular elements of the neural network that controls ingestive feeding have been identified. The results of 3 experiments demonstrate an interaction between odor input and ingestive feeding in that olfactory stimulation with behaviorally attractive odors summed with tactile stimulation from plain agar to produce ingestion of plain agar. Agar ingestion did not occur in the absence of attractive odor stimulation. The adequacy of odor stimulation to trigger agar ingestion was altered by associative learning. Innately attractive odors rendered repellent by associative learning no longer triggered agar ingestion, whereas innately repellent odors rendered attractive by conditioning triggered agar ingestion. The newly discovered feeding command cells in the Limax cerebral ganglion are a logical cellular locus for this interaction.

Animals↗
PubMed1992

Biochemical activities of the parA partition protein of the P1 plasmid.

The unit-copy P1 plasmid depends for stability on a plasmid-encoded partition region called par, consisting of the parA and parB genes and the parS site. ParA is absolutely required for partition, but its partition-critical role is not known. Purified ParA protein is shown to possess an ATPase activity in vitro which is specifically stimulated by purified ParB protein and by DNA. ParA is responsible for regulation of expression of parA and parB, and purified ParA has an ATP-dependent, site-specific DNA binding activity which recognizes a sequence that overlaps the parA promoter. The role of the ATP-dependence of the binding activity, as well as other possible functions of the ATPase activity in partition, is discussed.

Adenosine Triphosphatases↗
PubMed1992

Expression of the mRNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain.

1. The gene for a mammalian Shaw K+ channel has recently been cloned and has been shown, by alternative splicing, to give rise to two different transcripts, Kv3.1 alpha and Kv3.1 beta. To determine whether these channels are associated with specific types of neurons and to determine whether or not the alternately spliced K+ channel variants are differentially expressed, we used ribonuclease (RNase) protection assays and in situ hybridization histochemistry to localize the specific subsets of neurons containing Kv3.1 alpha and Kv3.1 beta mRNAs in the adult and developing rat brain. 2. In situ hybridization histochemistry revealed a heterogeneous expression pattern of Kv3.1 alpha mRNA in the adult rat brain. Highest Kv3.1 alpha mRNA levels were expressed in the cerebellum. High levels of hybridization were also detected in the globus pallidus, subthalamus, and substantia nigra reticulata. Many thalamic nuclei, but in particular the reticular thalamic nucleus, hybridized well to Kv3.1 alpha-specific probes. A subpopulation of cells in the cortex and hippocampus, which by their distribution and number may represent interneurons, were also found to contain high levels of Kv3.1 alpha mRNA. In the brain stem, many nuclei, including the inferior colliculus and the cochlear and vestibular nuclei, also express Kv3.1 alpha mRNA. Low or undetectable levels of Kv3.1 alpha mRNA were found in the caudate-putamen, olfactory tubercle, amygdala, and hypothalamus. 3. Kv3.1 beta mRNA was also detected in the adult rat brain by both RNase protection assays and by in situ hybridization experiments. Although the beta splice variant is expressed at lower levels than the alpha species, the overall expression pattern for both mRNAs is similar, indicating that both splice variants co-expressed in the same neurons. 4. The expression of Kv3.1 alpha and Kv3.1 beta transcripts was examined throughout development. Kv3.1 alpha mRNA is detected as early as embryonic day 17 and then increases gradually until approximately postnatal day 10, when there is a large increase in the amount of Kv3.1 alpha mRNA. Interestingly, the expression of Kv3.1 beta mRNA only increases gradually during the developmental time frame examined. Densitometric measurements indicated that Kv3.1 alpha is the predominant splice variant found in neurons of the adult brain, whereas Kv3.1 beta appears to be the predominant species in embryonic and perinatal neurons. 5. Most of the neurons that express the Kv3.1 transcripts have been characterized electrophysiologically to have narrow action potentials and display high-frequency firing rates with little or no spike adaptation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Hypothalamic gonadotropin-releasing hormone secretion and follicle-stimulating hormone dynamics during the luteal-follicular transition.

To define the precise neuroendocrine characteristics of the luteal-follicular transition, 11 normal women underwent 12 frequent sampling studies at 10-min intervals for 48 h at various points during the transition from one cycle to the next. Daily blood samples captured both the preceding and subsequent LH surges, so that studies could be characterized in relation to the preceding LH peak (LH+), the subsequent LH peak (LH-), and menses (M). In the frequent sampling study, LH and FSH were measured in all samples, and estradiol (E2) and progesterone (P) were measured in 2-h pools. The frequency of pulsatile LH secretion increased 4.5-fold over an 8-day period spanning the luteal-follicular transition. This increase in LH pulse frequency was strongly related to the preceding LH peak (r = 0.82; P less than 0.00001), but was not at all related to the onset of menses. When the temporal markers (i.e. LH+, LH-, and M) were removed from the analysis, LH pulse frequency was inversely related to the log of serum P (r = 0.50; P less than 0.005), but not E2. FSH levels increased both within the individual studies (P less than 0.005) and in the group as a whole over the duration of the luteal-follicular transition. Mean FSH rose 3.5-fold compared to less than a 2-fold increase in mean LH. As with LH pulse frequency, the increase in FSH was most strongly related to the preceding LH peak, but was also significantly associated with the subsequent LH peak and the onset of menses. The relationship between FSH and the number of days from the preceding LH peak is even better fit by a second degree polynomial, which revealed an abrupt increase in LH beginning at LH+11. With the temporal markers excluded, the increase in FSH related only to LH pulse frequency (r = 0.62; P less than 0.001). FSH was not statistically related to the decreases in P or E2, which are also key variables at this stage of the menstrual cycle. We reached the following conclusions. 1) A dramatic increase in LH pulse frequency, and by inference GnRH pulse frequency, accompanies the selective rise in FSH levels during the luteal-follicular transition of the normal menstrual cycle. 2) Both the increase in GnRH pulse frequency and the rise in FSH levels during this transition are strongly related to the preceding LH peak, while the clinical marker of menses is a relatively poor indicator of these events.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Biocytin as a retrograde tracer in the mammalian visual system.

We have successfully used biocytin as a retrograde tracer in the mammalian visual system. Retinal ganglion cells, pyramidal and stellate cortical neurons were labelled. Both pressure injections and gel implants were used successfully for retrograde labelling. Biocytin was detected using avidin conjugates and horseradish peroxidase histochemistry. Retrograde filling with biocytin proved to be more reliable and to allow better morphological resolution than other commonly used neurotracers such as horseradish peroxidase. The fine details of cell morphology observable by this method are comparable in many cases to the results obtained with intracellular tracer injections. The morphological resolution obtained with this method allows the study of brain microcircuits using extracellular deposits of biocytin.

Animals↗
PubMed1991

Synaptic background activity influences spatiotemporal integration in single pyramidal cells.

The standard one-dimensional Rall cable model assumes that the electrotonic structure of neurons does not change in response to synaptic input. This model is used in a great number of both theoretical and anatomical-physiological structure-function studies. In particular, the membrane time constant, tau m, the somatic input resistance, Rin, and the electrotonic length are used to characterize single cells. However, these studies do not take into account that neurons are embedded in a network of spontaneously active cells. Synapses from these cells will contribute significantly to the membrane conductance, especially if recent evidence of very high specific membrane resistance, Rm = 100 k omega.cm2, is taken into account. We numerically simulated the electrical behavior of an anatomically reconstructed layer V cortical pyramidal cell receiving input from 4000 excitatory and 1000 inhibitory cells firing spontaneously at 0-7 Hz. We found that, over this range of synaptic background activity, tau m and Rin change by a factor of 10 (80-7 msec, 110-14 M omega) and the electrotonic length of the cell changes by a factor of 3. We show that this significantly changes the response of the cell to temporal desynchronized versus temporal synchronized synaptic input distributed throughout the neuron. Thus, the global activity of the network can control how individual cells perform spatial and temporal integration.

Action Potentials↗
PubMed1991

Identification and localization of a dogfish homolog of human cystic fibrosis transmembrane conductance regulator.

Chloride channels in the apical plasma membrane of cells in the dogfish rectal gland have served as a model system for the study of regulation of chloride flux by changes in intracellular cyclic AMP levels. Similar regulation by cyclic AMP has been described for channels in cells of human secretory epithelia where defective regulation by cyclic AMP-dependent protein phosphorylation is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). We have isolated a cDNA clone from the rectal gland encoding a protein that is 72% identical to the human CFTR. One of the major phosphorylation sites in CFTR is absent in the dogfish protein. The dogfish protein has, however, four additional putative substrate sites for the cyclic AMP-dependent protein kinase. A peptide antibody, which was raised against an amino acid sequence common to both the human and dogfish CFTR sequences, recognizes proteins with similar molecular masses (160 kDa) in the dogfish gland and in mammalian lung. Immunolocalization studies with this antibody show that the putative dogfish CFTR is localized to the apical membrane of cells lining the lumen of the rectal gland.

Amino Acid Sequence↗
PubMed1991

Opening the grey box.

The single neurone has been the guiding light for generations of neuroscientists. Now there are signs from experimental and theoretical work on the neocortex that we are on the threshold of a revolution in which the hegemony of the single neurone will be replaced by much more circuit-oriented concepts. We consider here why traditional views of the significance of single neurones are fading in power, and consider the problem of deciding on the form of a new order.

Action Potentials↗
PubMed1991

An intracellular analysis of the visual responses of neurones in cat visual cortex.

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity.

Action Potentials↗
PubMed1991

Mechanisms of inhibition in cat visual cortex.

1. Neurones from layers 2-6 of the cat primary visual cortex were studied using extracellular and intracellular recordings made in vivo. The aim was to identify inhibitory events and determine whether they were associated with small or large (shunting) changes in the input conductance of the neurones. 2. Visual stimulation of subfields of simple receptive fields produced depolarizing or hyperpolarizing potentials that were associated with increased or decreased firing rates respectively. Hyperpolarizing potentials were small, 5 mV or less. In the same neurones, brief electrical stimulation of cortical afferents produced a characteristic sequence of a brief depolarization followed by a long-lasting (200-400 ms) hyperpolarization. 3. During the response to a stationary flashed bar, the synaptic activation increased the input conductance of the neurone by about 5-20%. Conductance changes of similar magnitude were obtained by electrically stimulating the neurone. Neurones stimulated with non-optimal orientations or directions of motion showed little change in input conductance. 4. These data indicate that while visually or electrically induced inhibition can be readily demonstrated in visual cortex, the inhibition is not associated with large sustained conductance changes. Thus a shunting or multiplicative inhibitory mechanism is not the principal mechanism of inhibition.

Action Potentials↗
PubMed1991

Excitation by geniculocortical synapses is not 'vetoed' at the level of dendritic spines in cat visual cortex.

1. We used anatomical methods to examine whether the geniculocortical afferent input to dendritic spines could be gated or 'vetoed' by an inhibitory input to the same spine. 2. Physiologically identified X- and Y-type afferents were injected intra-axonally with horseradish peroxidase (HRP), processed, and drawn under the light microscope. Selected regions of the terminal arbors were then serially sectioned for examination under the electron microscope. 3. Three-dimensional reconstructions of thirty-nine HRP-filled terminal boutons forming fifty asymmetric (type 1) synapses showed that thirty-one synapses were on the heads of dendritic spines. Only two of thirty-one spine heads received an additional symmetric (type 2) synapse, which is presumed to be inhibitory. 4. Examination of twenty-three boutons from two clutch cells (a GABA (gamma-aminobutyric acid)-ergic smooth cell) that form symmetric (type 2) synapses on spines indicated that their preferred location was opposite the asymmetric synapse on the head of the spine. Synaptic input to the necks of spines appears rare. 5. We conclude that most of the excitation provided by the geniculocortical afferent input to the heads of spines cannot be gated or vetoed by inhibition at the level of the spine.

Animals↗
PubMed1991

A functional microcircuit for cat visual cortex.

1. We have studied in vivo the intracellular responses of neurones in cat visual cortex to electrical pulse stimulation of the cortical afferents and have developed a microcircuit that simulates much of the experimental data. 2. Inhibition and excitation are not separable events, because individual neurones are embedded in microcircuits that contribute strong population effects. Synchronous electrical activation of the cortex inevitably set in motion a sequence of excitation and inhibition in every neurone we recorded. The temporal form of this response depends on the cortical layer in which the neurone is located. Superficial layer (layers 2+3) pyramidal neurones show a more marked polysynaptic excitatory phase than the pyramids of the deep layers (layers 5+6). 3. Excitatory effects on pyramidal neurones, particularly the superficial layer pyramids, are in general not due to monosynaptic input from thalamus, but polysynaptic input from cortical pyramids. Since the thalamic input is transient it does not provide the major, sustained excitation arriving at any cortical neurone. Instead the intracortical excitatory connections provide the major component of the excitation. 4. The polysynaptic excitatory response would be sustained well after the stimulus, were it not for the suppressive effect of intracortical inhibition induced by the pulse stimulation. 5. Intracellular recording combined with ionophoresis of gamma-aminobutyric acid (GABA) agonists and antagonists showed that intracortical inhibition is mediated by GABAA and GABAB receptors. The GABAA component occurs in the early phase of the impulse response. It is reflected in the strong hyperpolarization that follows the excitatory response and lasts about 50 ms. The GABAB component occurs in the late phase of the response, and is reflected in a sustained hyperpolarization that lasts some 200-300 ms. Both components are seen in all cortical pyramidal neurones. However, the GABAA component appears more powerful in deep layer pyramids than superficial layer pyramids. 6. The microcircuit simulates with good fidelity the above data from experiments in vivo and provides a novel explantation for the apparent lack of significant inhibition during visual stimulation. The basic circuit may be common to all cortical areas studied and thus the microcircuit may be a 'canonical' microcircuit for neocortex.

Animals↗
PubMed1991

Fine-structure analysis of the P1 plasmid partition site.

P1 plasmid partition requires two plasmid-encoded Par proteins and a cis-acting site. The site, parS, lies in a region consisting of a 13-bp palindrome and an adjacent AT-rich sequence. A series of point mutations were analyzed for their effects on partition site activity. The results indicated that only the left arm of the palindrome and some adjacent bases were needed. The limits of the functional site were further refined to a maximum of 22 bp, which includes binding sites for the P1 ParB protein. Mutations in the 22-bp site cause concomitant defects in partition and the ability to exert partition-mediated incompatibility. Like the region immediately to the left of the 22-bp region, the right arm of the palindrome is not essential for partition but does contain information that affects the specificity of incompatibility.

Bacterial Proteins↗
PubMed1991

Precursors of alpha-inhibin modulate follicle-stimulating hormone receptor binding and biological activity.

Although several forms of monomeric alpha-inhibin have been isolated from follicular fluid, no biological function has yet been ascribed to these posttranslationally processed forms of the alpha-subunit precursor protein. Moreover, previous studies of a FSH receptor binding competitor (FRBC) isolated and characterized from porcine follicular fluid (pFF) suggested certain biochemical similarities between this protein and alpha-inhibin precursors. We, therefore, investigated the hypothesis that alpha-inhibin and/or its precursors might represent autocrine and/or paracrine modulators of FSH action in the ovary, accounting for some of this FRBC activity and thereby exerting some degree of regulation over follicular maturation. Three separate sources of alpha-inhibin proteins were investigated for FRBC activity, including pFF, human FF (hFF), and a 293 cell line into which the full-length human alpha-inhibin cDNA had been stably transfected. Conditioned medium from these transfected cells contained several forms of alpha-inhibin precursors as well as mature alpha-inhibin, but no beta-subunit or intact inhibin. alpha-Inhibin proteins from all three sources, purified by a variety of methods, including immunoaffinity chromatography on an anti-alpha-inhibin column, inhibited FSH binding to both natural tissue FSH receptors as well as recombinant rat FSH receptors expressed in 293 cells. Furthermore, dimeric inhibin and activin, medium from untransfected 293 cells, and non-alpha-inhibin-containing purification fractions were inactive in either assay. In addition, purified recombinant alpha-inhibin proteins were partial in vitro FSH antagonists in a bioassay in which cAMP generation from 293 cells expressing the recombinant FSH receptor is used as an index of FSH biological activity. These same fractions of hFF containing FRBC activity did not bind to LH receptors, thereby demonstrating receptor specificity for this activity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting with alpha-inhibin or FRBC antisera, a 57,000 mol wt protein was identified in FRBC-active fractions from all three sources, suggesting that the active moiety was the full-length alpha-inhibin precursor protein or a large mol wt fragment, but not mature alpha-inhibin. Lastly, all FRBC activity from all three sources was extracted by an alpha-inhibin immunoaffinity column and was recoverable upon elution. These results demonstrate that proteins derived from the alpha-inhibin precursor modulate FSH binding to its receptor as well as its biological activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗